At present, numerous therapeutic techniques are based on systemic delivery of therapeutic agents. Systemic delivery, however, is not well suited to the treatment of disease entities with a single site of interest. For example, systemic delivery necessitates exposing sites other than the site of interest to medication where the medication may have an adverse reaction. As a result, the agent concentration at the site of interest is often limited by the detrimental effects of the agent at distant sites. Moreover, sufficiently large quantities of agent within the entire volume of the body are required to obtain the desired effect at the desired site. Finally, the agent is exposed to degradation and elimination by an organ system(s) remote from the site of interest. In response to this recognition, numerous techniques and medical articles for the localized delivery of therapeutic agents to the body have been proposed.
Nitric oxide is a gaseous molecule produced constitutively in the body through the enzymatic degradation of L-arginine. Under conditions of oxidative stress, an induced nitric oxide is also produced. Nitric Oxide is a highly reactive free radical, properly represented by NO♦, however, for purposes of this patent application it will also be represented by “nitric oxide” and “NO”. Nitric oxide has been shown at lower doses to relax smooth muscle cells (including vascular smooth muscle cells), inhibit vascular smooth muscle cell proliferation, protect endothelial cells from apoptosis, provide anti-thrombogenic and antioxidant effects, and promote wound healing. At higher dosages, it ultimately becomes cytotoxic.
Local delivery of compounds that release or produce nitric oxide has been proposed. However, it is not presently known to locally and differentially deliver nitric oxide to the body. As will become clear below, local differential delivery of nitric oxide to the body is useful in connection with a number of therapeutic strategies.